Corticostriatal connectivity is central for many cognitive and motor processes, such as reinforcement or action initiation and invigoration. The cortical input to the striatum arises from two main cortical populations: intratelencephalic (IT) and pyramidal tract (PT) neurons. We report a previously unknown excitatory circuit, supported by a polysynaptic motif from PT neurons to cholinergic interneurons (ChIs) to glutamate-releasing axons, which runs in parallel to the canonical monosynaptic corticostriatal connection. This motif conveys a delayed second phase of excitation to striatal spiny projection neurons, through an acetylcholine-dependent glutamate release mechanism mediated by α4-containing nicotinic receptors, resulting in biphasic corticostriatal signals. These biphasic signals are a hallmark of PT, but not IT, corticostriatal inputs, due to a stronger relative input from PT neurons to ChIs. These results describe a previously unidentified circuit mechanism by which PT activity amplifies excitatory inputs to the striatum, with potential implications for behavior, plasticity, and learning.

Corticostriatal connectivity is central for many cognitive and motor processes, such as reinforcement or action initiation and invigoration. The cortical input to the striatum arises from two main cortical populations: intratelencephalic (IT) and pyramidal tract (PT) neurons. We uncovered a new feed-forward excitatory circuit, supported by a polysynaptic motif from PT neurons to cholinergic interneurons (ChIs) to excitatory inputs, which runs in parallel to the canonical monosynaptic corticostriatal connection. This new motif conveys a delayed second phase of excitation to striatal spiny projection neurons (SPNs), through an acetylcholine-dependent glutamate release mechanism, resulting in biphasic corticostriatal signals. These biphasic signals are a hallmark of PT, but not IT, corticostriatal inputs, due to a stronger relative input from PT neurons to ChIs. These results uncover a novel feed-forward circuit mechanism by which PT activity differentially gates excitatory inputs to the striatum, with potential implications for behavior, plasticity and learning.

Traumatic spinal cord injury (SCI) initiates a cascade of cellular events, culminating in irreversible tissue loss and neuroinflammation. After the trauma, the blood vessels are destroyed. The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, is disrupted, facilitating the infiltration of immune cells, and contributing to a toxic spinal microenvironment, affecting axonal regeneration. Understanding how the vascular constituents of the BSCB respond to injury is crucial to prevent BSCB impairment and to improve spinal cord repair. Here, we focus our attention on the vascular transcriptome at 3- and 7-days post-injury (dpi), during which BSCB is abnormally leaky, to identify potential molecular players that are injury-specific. Using the mouse contusion model, we identified Cd9 and Mylip genes as differentially expressed at 3 and 7 dpi. CD9 and MYLIP expression were injury-induced on vascular cells, endothelial cells and pericytes, at the injury epicentre at 7 dpi, with a spatial expression predominantly at the caudal region of the lesion. These results establish CD9 and MYLIP as two new potential players after SCI, and future studies targeting their expression might bring promising results for spinal cord repair.

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